Dr. LE Thi Nguyet Minh

Dr Le graduated from the National University of Singapore in 2005 with a Bachelor degree in Life Sciences. She further received a Ph.D. degree in Computational and Systems Biology from the Singapore-Massachusetts Institute of Technology (MIT) Alliance under the guidance of Prof. Bing Lim at the Genome Institute of Singapore and Prof. Harvey Lodish at the Whitehead Institute for Biomedical Research. From 2010 to 2015, she worked as a postdoctoral fellow with Prof. Judy Lieberman at Boston Children’s Hospital and Harvard Medical School in the USA. She joined the Department of Biomedical Sciences at City University of Hong Kong (CityU) as a tenure-track Assistant Professor in August 2015.

Dr Le is well recognised for her contributions to the field of microRNAs (miRNAs) and cancer biology. She was the first to identify a miRNA that regulates p53, an important tumor suppressor gene. This miRNA, miR-125b, was subsequently found to be a potent oncogenic miRNA in leukemia and many solid tumors. Dr Le characterised the anti-apoptotic functions of miR-125b in zebrafish embryos and mammalian cells. She demonstrated that this tiny RNA is dispensable for normal development as it regulates the delicate balance between cell death and growth by repressing the p53 gene network. Furthermore, during her postdoctoral training, Dr Le illustrated a novel mechanism of cancer crosstalk in which miRNAs secreted by metastatic breast cancer cells are delivered to non-metastatic cells via extracellular vesicles (EVs) and promote colonization of tumor cells in the lung. With these original findings, Dr Le’s articles have been cited over 1,200 times by researchers worldwide (link).

In addition to her interest in research, Dr Le also has a passion in education. She has organized the translation of “Molecular Cell Biology”, an American biology textbook by Lodish et al., into Vietnamese. As the project coordinator for the last 7 years, she has brought together the American authors, Vietnamese scholars, publishers, sponsors and hundreds of backers, to translate the most advanced knowledge in biology and promote science education in Vietnam. The first three volumes of the book are warmly welcomed by scientists and biology students in the country (link). Dr Le also organizes the Hong Kong RNA club for education in RNA research (link).

Dr Le was awarded several prestigious scholarships and fellowships during her studies such as the Lee Foundation study grant and the Singapore-MIT Alliance scholarship. She was one of the first three recipients of the L’Oréal Singapore for Women in Science National Fellowship broadcasted widely by the news in 2009 (link). During her training at Harvard Medical School, she was awarded the Jane Coffin Childs fellowship, a prestigious postdoctoral fellowship in the USA. She also won a number of competitive travel scholarships and poster awards at international conferences.

1. Determine how EVs mediate the interaction of tumor cells with microenvironmental cells to promote drug resistance and cancer metastasis.

Cancer is a critical disease with increasing incidence in Asia due to the increase in life expectancy and many other socioeconomic changes. In the last decades, early detection and treatment for certain types of cancers has significantly improved survival, but drug resistance and cancer metastasis remain the major cause of patient mortality. Metastasis is a multi-step process that involves the translocation of cancer cells to distant organs, and this requires tumor cells to constantly adapt to the changing microenvironments at each stage. During this process, tumor cells often release a large amount of bioactive molecules, including proteins, nucleic acids and lipids, into EVs which mediate their communication with other cells in the tumor niches and at distance sites. Although it is known that EVs secreted by tumor cells deliver bioactive molecules to various cell types, it is still unclear how these cargos alter recipient cell functions, thereby promoting metastasis. One of our research goals is to investigate the key molecular mechanisms of EV-mediated cancer communication in order to identify effective therapies against this disease.

 A representative live image of breast cancer cells secreting miR-200c in CD63-positive extracellular vesicles (Le et al, Journal of Clinical Investigation, 2014)

2. Develop EV-based therapies for cancer treatment

Based on the fact that EVs are natural vehicles of RNAs in intercellular communication, we have developed a strategy to harness EVs from red blood cells (RBCs) for delivery of RNA drugs to cancer cells. RBCs are readily available from blood banks and they release a large amount of EVs hence, it is easy to purify RBCEVs in large quantities without any expensive and labor-intensive cell culture. RBCEVs mediate robust delivery of therapeutic RNAs including antisense oligo nucleotides (ASOs), Cas9 mRNA and gRNAs to both leukemia cells and solid cancer cells for efficient miRNA inhibition and genome editing. Moreover, this delivery platform is safe as RBCEVs are devoid of DNA, growth factors, and toxic substances since human RBCs are enucleated primary cells. Our study is recently published in Nature Communications and patented by CityU. We are currently engineering RBCEVs further for specific delivery of gene therapies targeting different types of cancer.

Advantages of the RBCEV-based drug delivery platform (Le et al, Nature Research Bioengineering Community 2018)

• BMS8107 – Cancer Biology & Precision Medicine (graduate course, semester B, Dr Le is the course leader)
• BMS3007 – Good Laboratory Practice, Regulatory Compliance, and Ethical, Legal and Social Issues (undergraduate course, semester B, Dr Le is the course leader)
• BMS8111 – Immunology & Infectious Diseases (graduate course, semester B)
• BMS4001 – Medical Informatics and Laboratory Management (undergraduate course, semester B)
• BMS8110 – Genomics and Bioinformatics (graduate course, semester A)